Characterization of HULC, a novel gene with striking up-regulation in hepatocellular carcinoma, as noncoding RNA

被引:673
作者
Panzitt, Katrin
Tschernatsch, Marisa M. O.
Guelly, Christian
Moustafa, Tarek
Stradner, Martin
Strohmaier, Heimo M.
Buck, Charles R.
Denk, Helmut
Schroeder, Renee
Trauner, Michael
Zatloukal, Kurt
机构
[1] Med Univ Graz, Inst Pathol, A-8036 Graz, Austria
[2] Oridis Biomed, Graz, Austria
[3] Max F Perutz Labs, Vienna, Austria
[4] Med Univ Graz, Lab Expt & Mol Hepatol, Div Gastroenterol & Hepatol, Dept Internal Med, A-8036 Graz, Austria
基金
奥地利科学基金会;
关键词
D O I
10.1053/j.gastro.2006.08.026
中图分类号
R57 [消化系及腹部疾病];
学科分类号
摘要
Background & Aims: Recent studies have highlighted the role of noncoding RNAs (ncRNAs) in carcinogenesis, and suggested that this class of genes might be used as biomarkers in cancer. We searched the human genome for novel genes including ncRNAs related to hepatocellular carcinoma (HCC). Methods: An HCC-specific gene library was generated and screened for deregulated genes with 46 HCCs, 4 focal nodular hyperplasias, and 7 cirrhoses utilizing cDNA arrays. Sequencing of library clones identified a novel ncRNA as the most up-regulated gene in HCC. This gene was also cloned from different monkeys and characterized by quantitative RT-PCR, Northern blot analysis and in situ hybridization. Structural and functional studies included comparative sequence and protein expression analyses, quantitative RT-PCR of polysomal preparations, and siRNA-mediated knockdown experiments. Result: The most up-regulated gene in HCC named highly up-regulated in liver cancer (HULC) was characterized as a novel mRNA-like ncRNA. HULC RNA is spliced and polyadenlyated, and resembles the mammalian LTR transposon 1A. It does not contain substantial open reading frames, and no native translation product was detected. HULC is present in the cytoplasm, where it copurifies with ribosomes. siRNA-mediated knockdown of HULC RNA in 2 HCC cell lines altered the expression of several genes, 5 of which were known to be affected in HCC, suggesting a role for HULC in post-transcriptional modulation of gene expression. Conclusions: HULC is the first ncRNA with highly specific up-regulation in HCC. Because HULC was detected in blood of HCC patients, a potential use as novel biomarker can be envisaged.
引用
收藏
页码:330 / 342
页数:13
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